ArticleJournal of experimental & clinical cancer research : CR2017
Trastuzumab emtansine delays and overcomes resistance to the third-generation EGFR-TKI osimertinib in NSCLC EGFR mutated cell lines.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
- Targeted therapy for stage IA non-small cell lung cancer withTranslational lung cancer research · 2026Review
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- Antibody-drug conjugates in breast cancer: mechanisms of resistance and future therapeutic perspectives.NPJ breast cancer · 2025Review
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy.Frontiers in immunology · 2025Review
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Chemotherapy versus personalized therapy for EGFR mutant lung adenocarcinoma resistance to EGFR-tyrosine kinase inhibitors: a retrospective dual-center study.BMC pulmonary medicine · 2024Article
- Article
- The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors.Journal of hematology & oncology · 2024Review
- Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.Frontiers in immunology · 2024Review
- Nanocage-incorporated engineered destabilized 3'UTR ARE of ERBB2 inhibits tumor growth and liver and lung metastasis in EGFR T790M osimertinib- and trastuzumab-resistant and ERBB2-expressing NSCLC via the reduction of ERBB2.Frontiers in oncology · 2024Article
- SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators.Cancers · 2023Review
- SOS2 regulates the threshold of mutantbioRxiv : the preprint server for biology · 2023Article
- Making the Best Use of Available Weapons for the Inevitable Rivalry-Resistance to EGFR-TKIs.Biomedicines · 2023Review
- Trastuzumab-Emtansine and Osimertinib Combination Therapy to TargetJTO clinical and research reports · 2023Article
- Destabilized 3'UTR elements therapeutically degrade ERBB2 mRNA in drug-resistant ERBB2+ cancer models.Frontiers in genetics · 2023Article
- Novel systemic therapies in the management of tyrosine kinase inhibitor-pretreated patients with epidermal growth factor receptor-mutant non-small-cell lung cancer.Therapeutic advances in medical oncology · 2023Review
- Ado-tratuzumab emtansine beyond breast cancer: therapeutic role of targeting other HER2-positive cancers.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundOsimertinib is a third-generation EGFR-TKI with a high selective potency against T790M-mutant NSCLC patients. Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and HER-2 overexpression is a mechanism of resistance to osimertinib, this study was addressed to investigate the potential of combining osimertinib with trastuzumab emtansine (T-DM1) in order to improve the efficacy of osimertinib and delay or overcome resistance in NSCLC cell lines with EGFR activating mutation and with T790M mutation or HER-2 amplification.
methodsThe effects of osimertinib combined with T-DM1 on cell proliferation, cell cycle, cell death, antibody-dependent cell-mediated cytotoxicity (ADCC), and acquisition of osimertinib resistance was investigated in PC9, PC9-T790M and H1975 cell lines. The potential of overcoming osimertinib resistance with T-DM1 was tested in a PC9/HER2c1 xenograft model.
resultsT-DM1 exerted an additive effect when combined with osimertinib in terms of inhibition of cell proliferation, cell death and ADCC induction in PC9, PC9-T790M and H1975 cell lines. Combining osimertinib and T-DM1 using different schedules in long-term growth experiments revealed that the appearance of osimertinib-resistance was prevented in PC9-T790M and delayed in H1975 cells when the two drugs were given together. By contrast, when osimertinib was followed by T-DM1 an antagonistic effect was observed on cell proliferation, cell death and resistance acquisition. In xenograft models, we demonstrated that HER-2 amplification was associated with osimertinib-resistance and that T-DM1 co-administration is a potential strategy to overcome this resistance.
conclusionsOur data suggest that concomitant treatment with osimertinib and T-DM1 may be a promising therapeutic strategy for EGFR-mutant NSCLC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.